Aminoglycoside antibiotics are widely used in medicine and are known to be toxic to the kidney and ear with prolonged administration. Recently, these agents have been used as intravitreal injections in the treatment of bacterial endophthalmitis. Retinal toxicity has been observed after intravitreal injection of gentamicin, tobramycin, or kanamycin in experimental animals; the mechanism of this aminoglycoside retinal toxicity is unknown. I propose to characterize the retinal and retinal pigment epithelial (RPE) toxicity observed after administration of gentamicin, tobramycin, kanamycin, and streptomycin to animals by intravitreal, periocular, and systemic routes. Involvement will initially be characterized by light and electron microscopic examination of retina and RPE after graded doses of aminoglycosides with regard to 1) dosage level, 2) type of aminoglycoside, 3) route of administration, and 4) duration of treatment. Autoradiographic techniques will be used to document the presence of aminoglycoside in the intracellular deposits observed in preliminary studies. Additionally, eyes treated with aminoglycoside will be processed for quantitative evaluation of RPE phagocytosis relative to control eyes, as a measure of drug-induced abnormality in RPE function. This series of experiments has inerrelated objectives. At the subcellular level, it is important to investigate the alteration of lysosomal systems in the retina and RPE as a mechanism of drug toxicity, and to relate gentamicin retinopathy to gentamicin nephro- and ototoxicity within the context of drug-induced lipid storage disease. High clinical significance is provided by the increasing numbers of patients being exposed to aminoglycosides by intravitreal injection and infusion in the therapy of intraocular infections. In this context, only preliminary light microscopic evidence of gross retinal disorganization and pigmentation in rabbit eyes is available to guide the safety of clinical intraocular aminoglycoside therapy in humans; the potential for important delayed or less conspicuous retinal toxicity by these potent lipidosis-inducing antibiotics has not been evaluated.